Diseases

Treacher Collins affects an estimated 1 in 50,000 people.

When Treacher Collins results from mutations in the TCOF1 or POLR1D gene, it is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 60 percent of these cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In the remaining autosomal dominant cases, a person with TCS inherits the altered gene from an affected parent.When TCS is caused by mutations in the POLR1C gene, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

• People with TCS often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called an eyelid coloboma.
• Some individuals have additional eye abnormalities that can lead to vision loss.
• It also characterized by absent, small, or unusually formed ears.
• Hearing loss occurs in about half of all individuals with the problem; hearing loss is caused by defects of the three small bones in the middle ear, which transmit sound, or by underdevelopment of the ear canal.
• People with Treacher Collins usually have normal intelligence.

The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most individuals have:

• underdeveloped facial bones,
• particularly the cheek bones, and
• A very small jaw and chin (micrognathia).

Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.

There is currently no cure for TCS. Treatment is tailored to the specific needs of each child or adult. Ideally, treatment is managed by a multidisciplinary team of craniofacial specialists.Newborns may need special positioning or tracheostomy to manage the airway. Hearing loss may be treated with bone conduction amplification, speech therapy, and/or educational intervention.In many cases, craniofacial reconstruction is needed. Surgery may be performed to repair cleft palate, to reconstruct the jaw, or to repair other bones in the skull. The specific surgical procedures used and the age when surgery is performed depends on the severity of the abnormalities, overall health and personal preference.There are some possible treatments that are being investigated. Researchers are looking for ways to inhibit a protein called p53, which helps the body to kill off unwanted cells. In people with TCS, p53 is abnormally activated, leading to the loss of specific cells and ultimately causing features of TCS. It has been proposed that inhibiting the production of p53 (or blocking its activation) may help to treat affected people. However, more research is needed to determine if this type of treatment is effective and safe.Researchers are also studying the use of stems cells found in fat tissue to be used alongside surgery in people with TCS and other craniofacial disorders. Early studies have shown that surgical outcomes may be improved using these stem cells to help stimulate the regrowth of affected areas. However, this therapy is still experimental and controversial.

Mutations in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins. TCOF1 gene mutations are the most common cause of the disorder, accounting for 81 to 93 percent of all cases. POLR1C and POLR1D gene mutations cause an additional 2 percent of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown.The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into new proteins, which is essential for the normal functioning and survival of cells. Mutations in the TCOF1, POLR1C, or POLR1D gene reduce the production of rRNA. Researchers speculate that a decrease in the amount of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. The abnormal cell death could lead to the specific problems with facial development found in TCS. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Usually, people with TCS grow to become functioning adults with normal intelligence. With proper management, life expectancy is approximatelythe same as in the general population. In some cases, the prognosis depends on the specific symptoms and severity in the affected person. For example, very severe cases of TCS can cause perinatal death because of a compromised airway.

Treacher Collins is a condition that affects the development of bones and other tissues in the face.

Other names for TCS include:

• Franceschetti-Zwahlen-Klein syndrome
• Mandibulofacial dysostosis (MFD1)
• Treacher Collins-Franceschetti syndrome
• zygoauromandibular dysplasia

These resources address the diagnosis or management of TCS and may include treatment providers.

• Gene Review: Treacher Collins Syndrome
• Gene Tests: POLR1C-Related Treacher Collins Syndrome
• Gene Tests: POLR1D-Related Treacher Collins Syndrome
• Gene Tests: TCOF1-Related Treacher Collins Syndrome